Background: As many as 25% patients with a histological diagnosis of NSP at a thoracoscopic biopsy are eventually diagnosed with a malignancy, mostly mesothelioma, over the following months. Aim: to evaluate the value of pleural effusion levels of soluble mesothelin-related peptides (PE-SMRP) as a diagnostic tool in patients with histological diagnosis of NSP. Methods: All patients with an exudative pleural effusion and a histological diagnosis of NSP at thoracoscopic biopsies performed between Jenuary 2008 and December 2020 were followed for 18 months. A predefined cut-off level of 20 nM PE-SMRP, based on published data, was used to distinguish high- from low- PE-SMRP patients. A binary logistic regression was used to measure the relative risk of a later diagnosis of cancer. Results: Of the 185 patients with a diagnosis of NSP, 17 (9.2%) were diagnosed with cancer during follow-up (mean 6.38 months). A malignancy was diagnosed in 9 of the 15 high-PE-SMRP patients (60%), and in 8 of the 170 low-PE-SMRP patients (4.7%) (p<0.0001). High-PE-SMRP patients had a higher risk of being diagnosed with mesothelioma at follow-up (OR 31.2, 95% IC 8.5-114.7) (table 1).). Each nM increase in PE-SMRP increased the risk of a final diagnosis of mesothelioma by 1.07-fold (p<0.001). Conclusions: Patients with high levels of PE-SMRP are at increased risk of cancer after an initial histological diagnosis of NSP and might benefit from a closer follow-up.

Literature reports suggest that the host immune system may control Malignant Pleural Mesothelioma (MPM) growth, although its activity is limited by regulatory mechanisms. In this retrospective study, we analyzed the levels of pro-inflammatory (IL-1, IL-6, TNF), immune-regulatory (IL-10) and Th1/CTL-related cytokines (IL-12p70, IFN-γ) in the pleural exudate and their relationship with overall survival (OS) in MPM. Cytokines were quantified by multiplexed immunoassay. Concentrations were dichotomized with respect to the median value. Correlation between cytokine level and OS was assessed using univariate (Kaplan–Meier curves) and multivariate (Cox regression) analyses. Regarding outcome, tumor histology, therapies undergone and IFN-γ were independent prognostic factors of OS in a 72 MPM training cohort. Notably, high concentrations of IFN-γ halved death probability (HR of high vs low IFN-γ concentration = 0.491, 95%CI 0.3–0.8, p = 0.007). Also in patients with epithelioid histology and those receiving at least one line of therapy, high IFN-γ level was an independent factor predictive of OS (HR of high vs low IFN-γ concentration were 0.497, p = 0.007 and 0.324, p = 0.006, respectively). However, these data were not confirmed in a 77 MPM validation cohort, possibly due to the low IFN-γ levels encountered in this population, and the heterogeneous distribution of disease stages between the training and the validation cohorts. None of the other cytokines showed any effect on survival. High level of IFN-γ in pleural effusion may be associated with better survival in MPM patients and potentially serve as a prognostic biomarker. Larger prospective studies are needed to ascertain this hypothesis.

Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor survival rates. Therefore, it is essential to have effective biological markers predicting the course of the disease and prognosis. The aim of the present study was to highlight the prognostic significance of serum soluble mesothelin-related protein (Se-SMRP) in patients with MPM at diagnosis. Se-SMRP was determined in 60 patients using an ELISA commercial kit. Se-SMRP levels were subdivided into three tertile-based categories and in each category overall survival (OS) indexes were determined using the Kaplan-Meier and Cox regression analyses. The association between Se-SMRP levels and OS was also assessed by restricted cubic spline (RCS) analysis. No notable differences in the Kaplan-Meier probabilities were identified across the Se-SMRP categories (<0.66 nM, 0.66-1.46 nM, >1.46 nM) although an upward trend in death rate ratios (RR) was pointed out by comparing the higher (RR=1.95) and intermediate (RR=1.86) categories with the lower category (RR=1.00). In addition, such an increasing tendency, particularly when the biomarker exceeded 1.0 nM, was confirmed by an RCS function of Se-SMPR levels fitted to survival data using the Cox regression equation. The present study provided evidence in favor of a prognostic value of Se-SMRP in patients with MPM.

Programmed death-ligand 1 (PD-L1) protein plays a central role in the antitumor immune response, and appears to be a predictor of prognosis and efficacy for PD-L1 and programmed death 1 (PD-1) blockade therapy. The immunoregulatory role and prognostic impact of PD-L1 soluble form (sPD-L1) have been investigated in biological fluids of patients with different tumors. In malignant pleural mesothelioma (MPM), circulating sPD-L1 has been recently reported in patients’ sera, but no data are available in pleural effusions (PE). In our study, we evaluated the baseline expression levels of sPD-L1 in PE from 84 MPM patients and correlated them with PD-L1-status in matched tumors and patients’ overall survival (OS). sPD-L1 in PE was determined by ELISA and tumor PD-L1 by immunohistochemistry. Association of sPD-L1 with OS was estimated using the Cox regression model. We observed that sPD-L1 was variably expressed in all the PE and tended to be higher (by 30%) in patients with PD-L1-positive tumors (cut-off ≥ 1% stained cells) as compared to patients with PD-L1-negative tumors (geometric mean ratio = 1.28, P value = 0.288). sPD-L1 levels were significantly higher than those of sPD-1 (P value = 0.001) regardless of the MPM histotypes and they were positively correlated (r = 0.50, P value < 0.001). Moreover, high PE sPD-L1 concentrations were associated with a trend towards increased OS (hazard ratio 0.79, 95% CL 0.62–1.01, P value = 0.062). Our study documents the presence of sPD-L1 in PE of MPM patients, and suggests its possible biological and prognostic role in MPM.

Uomo di 61 anni, ex fumatore da 10 anni (pack-year 20), avvocato. All’anamnesi patologica pregresso ictusischemico nel 2010 senza esiti funzionali; diabete mellito in terapia con ipoglicemizzanti orali; cardiopatia ischemicacronica e pregressa angioplastica con posizionamento di stent su coronaria destra e marginale nel 2017; insufficienzarenale cronica secondaria a glomerulonefrite non precisata (non eseguita biopsia) evoluta fino allo stadiodi “end stage renal disease” e in trattamento emodialitico dal 2016, ora in fase di valutazione per trapianto renale. (...)

Background: TTP is one of the most effective pleurodesis methods in MPE but its optimal timing is not well-defined. While some groups perform thoracoscopic pleurodesis on the basis of endoscopic malignancy appearance during diagnostic medical thoracoscopy (MT), others wait for a definitive histological diagnosis. Aim: to evaluate if the presence of thoracoscopic features of neoplastic pleural involvement predicts the final diagnosis of malignancy and if TTP decreases PE recurrence in these cases. Methods: We included consecutive patients, among those referred for MT to two pleural units (1, Brescia and 2, Sarzana), with unilateral PE and an endoscopic appearance of malignant pleural involvement (nodules, masses, thickenings or mixed lesions). During MT all patients received pleural biopsies but only the patients referred to unit 1 received TTP. All cases with recurrent symptomatic PE that required drainage in the following 3 months were deemed as failures. Results: 62 patients (59 malignancies) were included (32/group). The positive predictive value of endoscopic appearance was 100% for nodules, masses and mixed lesions, 82.4% for thickenings. In group 1, the recurrence of PE was significantly lower than in group 2 (6.7% vs 56.7%, p<0.001; chi-square). The median time to recurrence of PE in the failure cases was 15 days. Conclusion: The accuracy of endoscopic appearance of malignancy was high, particularly in the presence of nodules, masses and mixed lesions. In the presence of these lesions, TTP might be warranted prior to final histological diagnosis to reduce recurrence of PE and the ensuing necessity for reintervention. Caution is necessary when thickening is the only feature.

The evaluation of progression in epithelioid malignant pleural mesothelioma (MPM) is currently performed by monitoring the tumor mass variation by radiological images.1Armato 3rd, S.G. Nowak A.K. Francis R.J. et al.Observer variability in mesothelioma tumor thickness measurements: defining minimally measurable lesions.J Thorac Oncol. 2014; 9: 1187-1194Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar In our previous letter of August 2018 in the Journal of Thoracic Oncology, we reported a case of MPM in which we observed a strong positive correlation between the levels of serum soluble mesothelin-related peptides (Se-SMRPs) and the thickness of the pleura measured by computed tomography (CT) scans.2Vigani A. Pistillo M.P. Giannoni U. et al.Use of serum mesothelin as an indicator of tumor progression in routine clinical practice of malignant pleural mesothelioma.J Thorac Oncol. 2018; 8: e143-e145Google Scholar, 3Robinson B.W. Creaney J. Lake R. et al.Mesothelin-family proteins and diagnosis of mesothelioma.Lancet. 2003; 362: 1612-1616Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 4Hollevoet K. Nackaerts K. Gosselin R. et al.Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma.J Thorac Oncol. 2011; 6: 1930-1937Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Thus, we suggested that Se-SMRP could be a useful marker to evaluate tumor progression in MPM. In the present letter, we have extended our study to other patients and confirmed the Se-SMRP/CT correlation by means of appropriate statistical analyses. We analyzed 10 MPM patients (6 epithelioid, 3 sarcomatoid, and 1 biphasic; 9 male; median age: 67.5 years) recruited at the Oncology Division, ASL5 La Spezia (Italy), between March 2011 and May 2017. Pleural effusion (PE) was present in eight patients at diagnosis whereas in two patients it appeared during the course of the disease. Three MPM patients received first-line therapy (pemetrexed plus cisplatin) and seven also had second-line therapy (pemetrexed plus cisplatin), no patient had extrapleural pneumonectomy, pleurectomy decortication, or treatment with hemithoracic radiotherapy. Se-SMRP levels and pleural thickness showed very similar trends during the follow-up period. However, this overlap was particularly accentuated in seven cases (Fig. 1A, cases 1-7). In contrast, in three cases, the trends diverged at certain time points, in particular those at which patients showed a strong increase in PE (case 8) or appearance of a PE not present at the diagnosis (cases 9 and 10) (data not shown). The association between Se-SMRP and pleural thickness was confirmed by a mixed-effects regression analysis which is able to properly address the within-patient correlation due to the repeated measurements (log-transformed) on the same subject over time.5Fitzmaurice G.M. Laird N.M. Ware J.H. Applied Longitudinal Analysis. Somerset. John Wiley & Sons, New Jersey2004Google Scholar After adjusting for age and disease stage at diagnosis, we observed a statistically significant (geometric) mean increase in pleural thickness of 110% (95% confidence interval [CI]: 16%–280%, p value = 0.014) per unit increase in log-SMRP (Fig. 1B). In conclusion, this study confirms our previous finding of a strong positive association between Se-SMRP and CT. Although CT provides direct information by images on the variation of MPM tumor volume and onset of new metastases, it cannot always be performed.1Armato 3rd, S.G. Nowak A.K. Francis R.J. et al.Observer variability in mesothelioma tumor thickness measurements: defining minimally measurable lesions.J Thorac Oncol. 2014; 9: 1187-1194Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar In contrast, testing Se-SMRP provides faster information and it can be performed together with other routine blood tests at each patient's visit. However, we must keep in mind the limitation of a Se-SMRP test, that is, the possibility that Se-SMRP levels could be influenced by the development of a new PE or by its volume variation. Se-SMRP is detected by the enzyme-linked immunosorbent assay that is a simple and rapid technique which can be performed on a single test, without requiring sophisticated equipment and high costs. Finally, we are strongly led to believe that the determination of Se-SMRP levels can be performed routinely and integrated to CT for monitoring the progression of MPM. This work was supported by grants from AIL (Sezione Francesca Lanzone) and Italian Ministry of Health (5 × 1000 funds 2015 to Dr. Fonana and Dr. Pistillo), Italy. The study was approved by the Liguria Region Ethics Committee (P.R. 207REG2014) and written informed consent was obtained from all patients.

Aim: This study evaluated the prognostic value of soluble mesothelin-related protein (SMRP) levels in pleural effusions (PE) from patients with pleural mesothelioma (MPM). Patients and Methods: SMRP level in PE was tested using an enzyme-linked immunosorbent assay (ELISA) in 109 patients with MPM at diagnosis before any treatment. The Kaplan–Meier method and the Cox regression were applied to compare overall survival probabilities across tertile categories of SMRP level. Results: No significant differences in Kaplan–Meier overall survival probabilities among the SMRP categories were found. A statistically non-significant trend for increased death rate ratio (RR) was computed (p=0.327) when the higher (>46.5 nM, RR=1.38) and intermediate (8.5-46.5 nM, RR=1.18) SMRP categories were compared to the lower category (<8.5 nM, RR=1.00). Cox regression modelling including a restricted cubic spline showed a moderately rising non-linear trend in death rate. Conclusion: The SMRP level in PE does not appear to have prognostic significance and its detection is not recommended in routine clinical management of patients with MPM.

Questo studio presenta i risultati preliminari del progetto del gruppo di lavoro intersocietario costituito dal Gruppo di Studio della Societa Italiana di Biochimica Clinica e Biologia Molecolare Clinica (SIBioC) “Liquidi cavitari” e l’Associazione Italiana Pneumologi Ospedalieri (AIPO). L’obiettivo del gruppo di lavoro e la definizione armonizzata e condivisa del percorso diagnostico basato sulla analisi del Liquido Pleurico (LP). Il progetto parte dalla ricognizione dello stato dell’arte, i cui risultati sono illustrati in questo articolo. La ricognizione, rivolta sia al personale operante in strutture di Medicina di Laboratorio e sia a clinici di Unita specializzate in Pneumologia, e stata condotta tra ottobre e dicembre 2016. E stato predisposto ed inviato online un questionario (21 quesiti) a tutti i soci di SIBioC e AIPO attraverso la piattaforma SurveyMonkey. All’iniziativa hanno partecipato 408 professionisti, di cui il 40,4% rappresentato da Specialisti di Medicina di Laboratorio, il 3,2% da Tecnici Sanitari di Laboratorio Biomedico, il 49,3% da Specialisti in Pneumologia e il 7,1% da operatori che non hanno dichiarato la qualifica professionale. Rispetto alla fase pre-analitica emergono alcune criticita ad esempio per il “quesito clinico”; sembra evidente la mancanza di una modalita di comunicazione strutturata fra clinici e laboratoristi (il 76,3% dei laboratoristi dichiara di non avere accesso al quesito clinico, malgrado l’86,6% degli Pneumologi dichiari che il quesito e invece formulato e trasmesso). Inoltre solo una percentuale inferiore al 40% riporta l’uso di contenitori appropriati per la raccolta del campione. Per quanto riguarda la scelta delle analisi di base e evidente buon accordo sulla necessita di eseguire sempre l’esame macroscopico del liquido, il pH, il dosaggio del glucosio, delle proteine totali e della Lattico Deidrogenasi (LDH) e l’esame citometrico; infine emerge l’importanza del calcolo dei rapporti di concentrazione tra LP e sangue venoso per le proteine totali e LDH. Nella gestione della fase analitica sono emersi come atteso i limiti nell’impiego di metodi verificati o validati, in particolare per il pH che solo nel 9,2% dei casi e determinato con il pHmetro. Il referto, in generale, appare carente e poco armonizzato. Nonostante le criticita emerse nel complesso, il sondaggio ha dato un feedback positivo; infatti ha messo in luce l’interesse su argomenti di nicchia come la gestione dell’LP stimolando la produzione di documenti condivisi fra clinica e laboratorio, attivita proposta dal 30,7% dei partecipanti.

Aim: Different characteristics have been proposed as prognostic indicators of MPM. Here, we describe some of the determinants of survival in patients with MPM managed at our Institution in Liguria, Italy. Methods: Data from consecutive patients diagnosed with MPM between 2003 and 2016 were collected. Cox regression models and Kaplan-Meier curves were analysed with SPSS. Results: During the study period, 369 patients were diagnosed with MPM. Kaplan-Meier analysis showed a significant difference in terms of median survival between males and females (358 vs. 475 days), and among different histological types (467, 193 and 391 days, for epithelioid, fibrous sarcomatoid and biphasic, respectively). No statistically significant difference was observed between patients with and without an occupational exposure to asbestos. The table shows the results of the Cox proportional hazard regression models. Conclusions: As expected, epithelioid histology and younger age at diagnosis were associated with a significantly better prognosis. In contrast to data previously reported by others, there was a significant increase in life expectancy in patients diagnosed more recently, likely reflecting the improvement in therapeutic approaches. Professional asbestos exposure did not influence survival in our series.

Donna di 83 anni, ex fumatrice da 10 anni (30 packs/year), ex insegnante di lettere, con storia di quadrantectomia mammaria sinistra per adenocarcinoma ER e Pgr positivo nel 2010, seguita da CT e RT. Ripresa di malattia in sede linfonodale e scheletrica nel 2016, ha fatto terapia con fulvestrant e acido zoledronico e poi vinorelbina e capecitabina. Nel 2017 in seguito a riscontro di CEA serico molto elevato (oltre 200 ng/mL) ha eseguito ulteriori accertamenti e la colonscopia ha evidenziato lesione a manicotto del sigma, con diagnosi istologica di adenocarcinoma. Nel frattempo dispnea ingravescente con riscontro di versamento pleurico a destra (Figura 1A) e PaO2 di 60 mmHg, per cui e stata ricoverata in Pneumologia il 24 novembre 2017 ed e stata sospesa la decisione terapeutica, protesi endo-intestinale, relativa all’adenocarcinoma del sigma. (...)

Malignant pleural mesothelioma (MPM) is a particularly aggressive tumor; it is asbestos related, arising from mesothelial cells of the pleura. In MPM conventional therapies are often ineffective, and early estimation of tumor progression acquires great clinical importance.1Opitz I. Friess M. Kestenholz P. et al.A new prognostic score supporting treatment allocation for multimodality therapy for malignant pleural mesothelioma: a review of 12 years’ experience.J Thorac Oncol. 2015; 10: 1634-1641Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar Generally, progression of the tumor is evaluated by using the radiological criteria of the Response Evaluation Criteria in Solid Tumors, which are based on linear measurements of target and nontarget lesions. However, the application of these criteria in MPM is more difficult than with other cancers because MPM develops as a diffuse or circumferential irregular pleural thickening.2Armato 3rd, S.G. Nowak A.K. Francis R.J. Kocherginsky M. Byrne M.J. Observer variability in mesothelioma tumor thickness measurements: defining minimally measurable lesions.J Thorac Oncol. 2014; 9: 1187-1194Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar The evaluation of tumor progression in MPM is currently performed by taking into account the thickness of the pleura, lymph nodes, and metastatic lesions. Soluble mesothelin-related peptides (SMRPs), which are expressed by normal mesothelial cells and overexpressed in MPM, can be secreted and detected in a patient’s serum (Se-SMRPs).3Robinson B.W. Creaney J. Lake R. et al.Mesothelin-family proteins and diagnosis of mesothelioma.Lancet. 2003; 362: 1612-1616Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar Se-SMRP levels have been found to be significantly increased in about 80% of patients with MPM,3Robinson B.W. Creaney J. Lake R. et al.Mesothelin-family proteins and diagnosis of mesothelioma.Lancet. 2003; 362: 1612-1616Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar, 4Grigoriu B.D. Chahine B. Vachani A. et al.Kinetics of soluble mesothelin in patients with malignant pleural mesothelioma during treatment.Am J Respir Crit Care Med. 2009; 179: 950-954Crossref PubMed Scopus (60) Google Scholar, 5Creaney J. Francis R.J. Dick I.M. et al.Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden.Clin Cancer Res. 2011; 17: 1181-1189Crossref PubMed Scopus (86) Google Scholar, 6Hollevoet K. Nackaerts K. Gosselin R. et al.Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma.J Thorac Oncol. 2011; 6: 1930-1937Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar have been associated with a worse prognosis,4Grigoriu B.D. Chahine B. Vachani A. et al.Kinetics of soluble mesothelin in patients with malignant pleural mesothelioma during treatment.Am J Respir Crit Care Med. 2009; 179: 950-954Crossref PubMed Scopus (60) Google Scholar, 5Creaney J. Francis R.J. Dick I.M. et al.Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden.Clin Cancer Res. 2011; 17: 1181-1189Crossref PubMed Scopus (86) Google Scholar, 6Hollevoet K. Nackaerts K. Gosselin R. et al.Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma.J Thorac Oncol. 2011; 6: 1930-1937Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar and have been approved by the U.S. Food and Drug Administration as a marker for the diagnosis and monitoring of epithelioid MPM. The possibility of using Se-SMRP detection to evaluate the tumor progression in MPM has been suggested by Robinson and et al. since 2003.3Robinson B.W. Creaney J. Lake R. et al.Mesothelin-family proteins and diagnosis of mesothelioma.Lancet. 2003; 362: 1612-1616Abstract Full Text Full Text PDF PubMed Scopus (481) Google Scholar Indeed, they found that Se-SMRP levels correlate with the tumor size, increasing during tumor progression and remaining constant in stable disease. Although all these findings have been confirmed by other reports,4Grigoriu B.D. Chahine B. Vachani A. et al.Kinetics of soluble mesothelin in patients with malignant pleural mesothelioma during treatment.Am J Respir Crit Care Med. 2009; 179: 950-954Crossref PubMed Scopus (60) Google Scholar, 5Creaney J. Francis R.J. Dick I.M. et al.Serum soluble mesothelin concentrations in malignant pleural mesothelioma: relationship to tumor volume, clinical stage and changes in tumor burden.Clin Cancer Res. 2011; 17: 1181-1189Crossref PubMed Scopus (86) Google Scholar, 6Hollevoet K. Nackaerts K. Gosselin R. et al.Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma.J Thorac Oncol. 2011; 6: 1930-1937Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar Se-SMRP detection has not yet entered routine clinical practice in many centers. In this letter, we provide an example of the routine application of Se-SMRPs in the evaluation of MPM progression. In particular, we report a correlation between Se-SMRP levels and computed tomography (CT) findings in a patient with epithelioid MPM. In August 2013, a 67-year-old man with history of asbestos exposure presented to our hospital with dyspnea and cough. Chest CT showed a diffuse irregular thickening of the right costal pleura associated with a metastatic subcarinal lymph node. Histopathological examination confirmed that the patient had epithelioid MPM (Union for International Cancer Control stage II and Eastern Cooperative Oncology Group performances status 1), which was treated with six cycles of cisplatin and pemetrexed (for 4 months). He died about 16 months after starting therapy. Before therapy, his Se-SMRP levels, the thickness of his pleura and the length of the short axis of his subcarinal lymph node were 1.23 nM (Fig. 1A), 1.9 mm, and 5.2 mm (Fig. 1B), respectively. In the subsequent 3 months, the patient’s Se-SMRP levels decreased slightly, reaching a minimum of 0.50 nM (see Fig. 1A), after which they continued increasing until his death. At the fifth month, his Se-SMRP level was 0.96 nM, the pleural thickness remained constant, and the subcarinal lymph node appeared further enlarged (the length of the short axis measured 9.3 mm). Fifteen days before the patient’s death, his Se-SMRP levels reached 7.71 nM and the thickness of the pleura and the length of the short axis of the subcarinal lymph node measured 9.4 mm and 20.5 mm, respectively (see Fig. 1A and B). We observed a strong positive correlation between the patient’s Se-SMRP levels and the radiological extent of his disease. In particular, by using the Spearman coefficient, we estimated a correlation of about 0.95 and 0.80 with the pleural thickness and length of the short axis of the subcarinal lymph node, respectively. This case report suggests that Se-SMRP level can be a useful marker to evaluate tumor progression, particularly when CT has not yet been performed or even to indicate that CT should be performed. In conclusion, detection of Se-SMRP provides useful information for management of patients with MPM. Se-SMRP is a practical marker that can be easily and quickly measured even for a single patient during routine checks. Thus, we believe that Se-SMRP level could be integrated with CT images for monitoring the progression of MPM. This study was approved by the Ethics Committee of the Liguria Region (P.R. 207REG2014).

The aim of this paper is to present the preliminary results of a joint project by SIBioC-AIPO working group on "Body cavities fluids". The main purpose of the working group is to achieve a harmonized and shared diagnostic pathway related to pleural fluid (PF) analysis. The multistep project begins with a state of the art analysis. A survey, sent to both laboratory medicine personnel and pneumologists, was conducted between October and December 2016. The questionnaire (21 questions) was made available through the web-based SurveyMonkey platform. Overall, 408 replies were collected, 40.4% from laboratory medicine specialists, 3.2% from laboratory technicians, 49.3% from pneumologists and 7.1% from professionals with non-specified qualification. Regarding the pre-analytical phase, the most critical issue resulted to be the clinical query, due to the lack of structured communication between clinicians and laboratory personnel. While over 76% of laboratory professionals stated that the working diagnosis was unavailable, 87% of pneumologists affirmed that the clinical question had been forwarded to the laboratory. An important issue was the widespread use of inappropriate containers for PF collection (60% of inappropriate tubes). Regarding the panel of tests, a satisfactory agreement was reached on the need to perform macroscopic analysis and cytometric evaluation, along with the assessment of pH, glucose, total proteins, lactate dehydrogenase and the respective ratios between PF and serum concentrations. As expected, the availability of verified or validated analytical methods, notably pH analysis, has emerged as a critical point. The layout of the laboratory report also needs improvements and better harmonization. Despite the many critical issues emerged from this survey, a positive feedback was reflected by a notable general interest on PF analysis, leading thus the way to produce a joint consensus document involving clinicians and laboratory personnel, as suggested by more than 30% of responders.